Exercise Induced Asthma
Conditions
Brief summary
The purpose of this study is to determine the effect of four weeks of treatment with two investigational drugs (oral versus inhaled administration) plus an inhaled medication in the treatment of airway constriction brought on by exercise in participants with asthma.
Interventions
DRUGMontelukast sodium
Montelukast 5 mg chewable tablet once daily
Salmeterol 50 mcg dry powder per actuation inhaled twice daily
DRUGFluticasone propionate
Fluticasone (50 mcg per actuation) 100 mcg inhaled twice daily
DRUGMontelukast matching placebo
Matching placebo to montelukast oral tablet administered once daily.
DRUGSalmeterol matching placebo
Matching placebo to salmeterol dry powder for inhalation administered twice daily
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 14 Years
Healthy volunteers
No
Inclusion criteria
* 6-14 year old children with a history of asthma for at least 12 months * must demonstrate airway constriction brought on by exercise
Exclusion criteria
* is taking any medications that are not allowed in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Post-exercise Percent (%) Fall in FEV1 | 4 weeks (Weeks 0 to 4 or Weeks 6 to 10) | The effect of four weeks of treatment with oral montelukast plus inhaled fluticasone, and inhaled salmeterol plus inhaled fluticasone on EIB as measured by the maximum post-exercise percent fall (relative to pre-exercise baseline) in FEV1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve for %-Change From Pre-exercise Baseline FEV1 in Liters (L), From 0 to 20 Minutes (AUC(0-20)) | 4 weeks (Weeks 0 to 4 or Weeks 6 to 10) | The effect of a four-week treatment course of oral montelukast plus inhaled fluticasone, compared to inhaled salmeterol plus inhaled fluticasone, on the extent and severity of EIB as measured by the area under the curve from 0 to 20 minutes (AUC0-20) for FEV1 percent change from pre-exercise baseline. |
| Maximum FEV1 % Predicted Following First Beta-agonist Use | 4 weeks (Weeks 0 to 4 or Weeks 6 to 10) | The effect of a four-week treatment course of oral montelukast plus inhaled fluticasone, compared to inhaled salmeterol plus inhaled fluticasone, on short-acting β-agonist bronchodilation as measured by the maximum FEV1 percent predicted following first β-agonist use. |
| Time to Recovery to Within 5% of Baseline FEV1 | 4 weeks (Weeks 0 to 4 or Weeks 6 to 10) | The effect of a four-week treatment course of oral montelukast plus inhaled fluticasone, compared to inhaled salmeterol plus inhaled fluticasone, on the extent and severity of EIB as measured by the time to recovery (to within 5 percent of the pre-exercise baseline FEV1) following a standardized exercise challenge. |
| Average (Avg) %-Change in FEV1 After First Beta (β)-Agonist Use and Prior to Second β-agonist Use | 4 weeks (Weeks 0 to 4 or Weeks 6 to 10) | The effect of a four-week treatment course of oral montelukast plus inhaled fluticasone, compared to inhaled salmeterol plus inhaled fluticasone, on the extent and severity of EIB as measured by the average percent change in FEV1 after first β-agonist intake and prior to second β-agonist use. |
Participant flow
Recruitment details
Multicenter Study (30 Ex-US sites) Study Initiation Date: December 22, 2005 Study Completion Date: November 14, 2008
Pre-assignment details
For randomization, patients fulfilled the following criteria: 1. Forced Expiratory Volume in one second (FEV1) ≥70% predicted while withholding beta (β)-agonist for at least 6 hours 2. Exercise-induced bronchoconstriction (EIB) showing FEV1 ≥15% reduction from baseline while on inhaled corticosteroids demonstrated twice during the run-in period.
Participants by arm
| Arm | Count |
|---|---|
| Montelukast / Salmeterol Period I- Montelukast 5 milligrams (mg) oral tablet once daily and Salmeterol matching placebo dry powder inhaler (DPI) twice daily for 4 weeks followed by a 2-week washout period (salmeterol matching placebo + montelukast matching placebo). Period II- Montelukast matching placebo oral tablet once daily and Salmeterol DPI 50 micrograms (mcg) twice daily for 4 weeks. Inhaled Fluticasone 100 mcg twice daily throughout the study. | 78 |
| Salmeterol / Montelukast Period I- Montelukast matching placebo oral tablet once daily and Salmeterol DPI 50 mcg twice daily for 4 weeks followed by a 2-week washout period (salmeterol matching placebo + montelukast matching placebo). Period II- Montelukast 5 mg oral tablet once daily and Salmeterol matching placebo DPI twice daily for 4 weeks. Inhaled Fluticasone 100 mcg twice daily throughout the study. | 76 |
| Total | 154 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period I | Patient did not meet inclusion criteria | 1 | 0 |
| Period I | Protocol Violation | 0 | 2 |
| Period I | Withdrawal by Subject | 2 | 0 |
| Period II | Patient did not perform Visit 6 exercise | 1 | 0 |
| Period II | Withdrawal by Subject | 2 | 0 |
| Washout Period | Patient did not meet inclusion criteria | 0 | 1 |
Baseline characteristics
| Characteristic | Montelukast / Salmeterol | Total | Salmeterol / Montelukast |
|---|---|---|---|
| Age, Continuous | 10.2 years STANDARD_DEVIATION 2 | 10.0 years STANDARD_DEVIATION 2 | 9.8 years STANDARD_DEVIATION 2 |
| Area Under the Curve from 0 to 20 minutes (AUC0-20) | 320.08 Percent times Minutes STANDARD_DEVIATION 208.62 | 318.93 Percent times Minutes STANDARD_DEVIATION 188.06 | 317.74 Percent times Minutes STANDARD_DEVIATION 165.71 |
| Avg %-change from pre-exercise baseline FEV1 after 1st β-agonist use & prior to 2nd β-agonist use | 1.36 Percent change from baseline STANDARD_DEVIATION 10.99 | 3.05 Percent change from baseline STANDARD_DEVIATION 11.05 | 4.78 Percent change from baseline STANDARD_DEVIATION 10.92 |
| Maximum FEV1 percent predicted | 99.88 Percent of predicted value STANDARD_DEVIATION 32.45 | 100.21 Percent of predicted value STANDARD_DEVIATION 25.49 | 100.54 Percent of predicted value STANDARD_DEVIATION 15.61 |
| Maximum percent fall in FEV1 after exercise | 24.77 Percent change from baseline STANDARD_DEVIATION 10.25 | 25.09 Percent change from baseline STANDARD_DEVIATION 9.65 | 25.42 Percent change from baseline STANDARD_DEVIATION 9.04 |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Black | 11 participants | 18 participants | 7 participants |
| Race/Ethnicity, Customized Other | 28 participants | 56 participants | 28 participants |
| Race/Ethnicity, Customized White | 38 participants | 79 participants | 41 participants |
| Sex: Female, Male Female | 35 Participants | 65 Participants | 30 Participants |
| Sex: Female, Male Male | 43 Participants | 89 Participants | 46 Participants |
| Time to recovery | 23.53 Minutes STANDARD_DEVIATION 10.53 | 22.53 Minutes STANDARD_DEVIATION 9.51 | 21.51 Minutes STANDARD_DEVIATION 8.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 150 | 21 / 150 |
| serious Total, serious adverse events | 1 / 150 | 1 / 150 |
Outcome results
Primary
Maximum Post-exercise Percent (%) Fall in FEV1
The effect of four weeks of treatment with oral montelukast plus inhaled fluticasone, and inhaled salmeterol plus inhaled fluticasone on EIB as measured by the maximum post-exercise percent fall (relative to pre-exercise baseline) in FEV1.
Time frame: 4 weeks (Weeks 0 to 4 or Weeks 6 to 10)
Population: The primary efficacy analysis was based on the full analysis set (FAS) population which included all randomized participants who took at least one dose of post randomization study drug and had a measurement for analysis available in both treatment periods of the cross-over design.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast | Maximum Post-exercise Percent (%) Fall in FEV1 | 10.57 Percent change from baseline |
| Salmeterol | Maximum Post-exercise Percent (%) Fall in FEV1 | 13.82 Percent change from baseline |
p-value: 0.00995% CI: [-5.66, -0.84]ANOVA
Secondary
Area Under the Curve for %-Change From Pre-exercise Baseline FEV1 in Liters (L), From 0 to 20 Minutes (AUC(0-20))
The effect of a four-week treatment course of oral montelukast plus inhaled fluticasone, compared to inhaled salmeterol plus inhaled fluticasone, on the extent and severity of EIB as measured by the area under the curve from 0 to 20 minutes (AUC0-20) for FEV1 percent change from pre-exercise baseline.
Time frame: 4 weeks (Weeks 0 to 4 or Weeks 6 to 10)
Population: The secondary efficacy analysis was based on the FAS population which included all randomized participants who took at least one dose of post randomization study drug and had a measurement for analysis available in both treatment periods of the cross-over design.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast | Area Under the Curve for %-Change From Pre-exercise Baseline FEV1 in Liters (L), From 0 to 20 Minutes (AUC(0-20)) | 116.04 Percent times Minutes |
| Salmeterol | Area Under the Curve for %-Change From Pre-exercise Baseline FEV1 in Liters (L), From 0 to 20 Minutes (AUC(0-20)) | 168.75 Percent times Minutes |
p-value: 0.00695% CI: [-89.76, -15.66]ANOVA
Secondary
Average (Avg) %-Change in FEV1 After First Beta (β)-Agonist Use and Prior to Second β-agonist Use
The effect of a four-week treatment course of oral montelukast plus inhaled fluticasone, compared to inhaled salmeterol plus inhaled fluticasone, on the extent and severity of EIB as measured by the average percent change in FEV1 after first β-agonist intake and prior to second β-agonist use.
Time frame: 4 weeks (Weeks 0 to 4 or Weeks 6 to 10)
Population: The secondary efficacy analysis was based on the FAS population which included all randomized participants who took at least one dose of post randomization study drug and had a measurement for analysis available in both treatment periods of the cross-over design.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast | Average (Avg) %-Change in FEV1 After First Beta (β)-Agonist Use and Prior to Second β-agonist Use | 6.51 Percent change from baseline |
| Salmeterol | Average (Avg) %-Change in FEV1 After First Beta (β)-Agonist Use and Prior to Second β-agonist Use | 2.72 Percent change from baseline |
p-value: <0.00195% CI: [2.28, 5.32]ANOVA
Secondary
Maximum FEV1 % Predicted Following First Beta-agonist Use
The effect of a four-week treatment course of oral montelukast plus inhaled fluticasone, compared to inhaled salmeterol plus inhaled fluticasone, on short-acting β-agonist bronchodilation as measured by the maximum FEV1 percent predicted following first β-agonist use.
Time frame: 4 weeks (Weeks 0 to 4 or Weeks 6 to 10)
Population: The secondary efficacy analysis was based on the FAS population which included all randomized participants who took at least one dose of post randomization study drug and had a measurement for analysis available in both treatment periods of the cross-over design.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Montelukast | Maximum FEV1 % Predicted Following First Beta-agonist Use | 104.03 Percent of predicted value |
| Salmeterol | Maximum FEV1 % Predicted Following First Beta-agonist Use | 99.92 Percent of predicted value |
p-value: <0.00195% CI: [2.58, 5.64]ANCOVA
Secondary
Time to Recovery to Within 5% of Baseline FEV1
The effect of a four-week treatment course of oral montelukast plus inhaled fluticasone, compared to inhaled salmeterol plus inhaled fluticasone, on the extent and severity of EIB as measured by the time to recovery (to within 5 percent of the pre-exercise baseline FEV1) following a standardized exercise challenge.
Time frame: 4 weeks (Weeks 0 to 4 or Weeks 6 to 10)
Population: The secondary efficacy analysis was based on the FAS population which included all randomized participants who took at least one dose of post randomization study drug and had a measurement for analysis available in both treatment periods of the cross-over design.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Montelukast | Time to Recovery to Within 5% of Baseline FEV1 | 5.9 minutes |
| Salmeterol | Time to Recovery to Within 5% of Baseline FEV1 | 11.1 minutes |
p-value: 0.03595% CI: [1.02, 1.55]Cox Proportional Hazards Model